The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study

• Sponsor: Jennifer Cowger , MD, MS (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01102140
• Collaborator: POM Wonderful LLC (Industry)
• Enrollment: 20
• Locations: 2
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 10
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This blinded, controlled study will examine the impact of pomegranate polyphenol extract (POMx, from Pom Wonderful, LLC), 1000mg on cardiomyopathy in subjects with chronic renal insufficiency.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy; Heart Failure	Drug: POMx, pomegranate polyphenol extract; Drug: Sugar Pill	Phase 2

Detailed Description

Heart failure (HF) is a disease of great prevalence in the U.S. with an associated high morbidity and mortality. In individuals with concomitant chronic renal insufficiency (CRI), outcomes are even worse due to pharmaceutical under treatment and higher baseline levels of oxidative stress. Reactive oxygen species (ROS) are generated during mechanoenergetic uncoupling and can cause myocardial protein, lipid, and DNA damage, leading to the development of HF. One means of preventing the progression of HF may be through ROS reduction or an improvement in systemic or local oxidative stress handling. In this randomized, single blind placebo-controlled pilot study, we hypothesize that 12 weeks of treatment with oral pomegranate extract (POMx) will lead to a reduction in oxidative stress (as assessed by measuring thiobarbituric acid-reactive substances, F8-isoprostanes, and glutathione) in subjects (n=30) with cardiomyopathy (LVEF ≤40%) and CRI (GFR <60 ml/hr). Secondary aims include assessing the impact of POMx on myocardial remodeling and endothelial dysfunction by measuring serum collagen levels and asymmetric dimethylarginine, respectively. Findings from this study will serve as pilot data for a larger randomized trial of longer term POMx therapy in subjects with cardiomyopathy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: The participant will either receive POMx or matching placebo (sugar pill)
• Primary Purpose: Treatment
• Official Title: The Impact of Pomegranate (Punica Granatum) Polyphenol Extract on Oxidative Stress, Ventricular Remodeling and Endothelial Function in Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: May 31, 2013
• Actual Study Completion Date: May 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: POMx 15 subjects will received 1000 mg of oral POMx for 12 weeks.	Drug: POMx, pomegranate polyphenol extract; 1000 mg orally once daily.
Placebo Comparator: Control- sugar Pill 15 subjects will receive a matching sugar pill for 12 weeks.	Drug: Sugar Pill; Matching sugar pill

Outcome Measures

Primary Outcome Measures

1. Thiobarbituric Reactive Substances (TBARS) [baseline and after 12 weeks]

   This is a serum marker of oxidative stress.

Secondary Outcome Measures

1. F-8 Isoprostanes [Baseline and 12 weeks]

   This is a serum marker of oxidative stress.

2. Procollagen Types I (PINP) and III (PIIINP) [baseline and 12 weeks]

   This is a serum marker of collagen turnover (fibrosis/scar formation).

3. Asymmetric Dimethylarginine (ADMA) [baseline and 12 weeks]

   ADMA is a serum enzyme involved in metabolism of endothelium derived nitric oxide (NO). NO's has an important role in maintaining endothelial homeostasis. Elevated ADMA levels suggest impaired endothelial function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult subjects (≥21 years of age) with cardiomyopathy (ejection fraction ≤40%) of at least 1 year duration and CRI (GFR <60 cc/hr for at least 3 months) will be eligible for enrollment.

• Subjects must have New York Heart Association (NYHA) functional class I-III symptoms and be on stable doses of HF evidence-based therapies (β-blocker, ACE inhibitor or ARBs, aldosterone inhibitor [if appropriate]) for at least 3 months or have a documented contraindication or intolerance to such therapy

Exclusion Criteria:

• Subjects admitted to a hospital for acute myocardial infarction (defined as positive troponins) or HF exacerbation within the last 6 months will not be eligible for enrollment.

• Subjects on warfarin or rosuvastatin will also be excluded.

• Other exclusion criteria are as follows:

• HF that is deemed to be congenital or infiltrative in etiology

• the presence of a life-threatening illness with a projected survival ≤6 months; ongoing infection

• pregnancy

• inability to follow-up

• end-stage renal disease requiring dialysis

• renal transplant listing

• recent (within last 6 months) POMx use or intake >8 ounces daily of pomegranate juice

• known hypersensitivity to any fruit in the Punicaceae family

• connective tissue or collagen vascular disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Health Systems	Ann Arbor	Michigan	United States	48109
2	University of Michigan Health System	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• Jennifer Cowger , MD, MS
• POM Wonderful LLC

Investigators

• Principal Investigator: Jennifer C Matthews, MD, MS, Univeristy of Michigan Health System
• Study Chair: Bertram Pitt, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Cowger , MD, MS, Assistant Professor, study PI, University of Michigan
• ClinicalTrials.gov Identifier: NCT01102140
• Other Study ID Numbers: IMPROVEHF
• First Posted: Apr 13, 2010
• Last Update Posted: Jul 14, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Jennifer Cowger , MD, MS, Assistant Professor, study PI, University of Michigan: Cardiomyopathy; Heart Failure
• Additional relevant MeSH terms: Renal Insufficiency; Heart Failure; Cardiomyopathies

Study Results

Participant Flow

Arm/Group Title	POMx	Control- Sugar Pill
Arm/Group Description	The POMx subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
Period Title: Overall Study
STARTED	13	7
COMPLETED	10	5
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	POMx	Control- Sugar Pill	Total
Arm/Group Description	The POMx subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill	Total of all reporting groups
Overall Participants	13	7	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 76.9%	5 71.4%	15 75%
>=65 years	3 23.1%	2 28.6%	5 25%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	58	57
Sex: Female, Male (Count of Participants)
Female	0 0%	2 28.6%	2 10%
Male	13 100%	5 71.4%	18 90%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 7.7%	0 0%	1 5%
White	12 92.3%	6 85.7%	18 90%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 14.3%	1 5%
Region of Enrollment (participants) [Number]
United States	13 100%	7 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Thiobarbituric Reactive Substances (TBARS)
Description	This is a serum marker of oxidative stress.
Time Frame	baseline and after 12 weeks

Outcome Measure Data

Analysis Population Description

Serum samples were obtained and frozen but never analyzed to obtain isoprostane values due to PI departure from study center prior to any batches being sent for analysis.

Arm/Group Title	POMx	Control- Sugar Pill
Arm/Group Description	The POMx subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
Measure Participants	0	0

2. Secondary Outcome

Title	F-8 Isoprostanes
Description	This is a serum marker of oxidative stress.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Serum samples were obtained and frozen but never analyzed to obtain isoprostane values due to PI departure from study center prior to any batches being sent for analysis

Arm/Group Title	POMx	Control- Sugar Pill
Arm/Group Description	The POMx subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
Measure Participants	0	0

3. Secondary Outcome

Title	Procollagen Types I (PINP) and III (PIIINP)
Description	This is a serum marker of collagen turnover (fibrosis/scar formation).
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Serum samples were obtained and frozen but never analyzed to obtain procollagen values due to PI departure from study center prior to any batches being sent for analysis

Arm/Group Title	POMx	Control- Sugar Pill
Arm/Group Description	The POMx subjects will receive 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
Measure Participants	0	0

4. Secondary Outcome

Title	Asymmetric Dimethylarginine (ADMA)
Description	ADMA is a serum enzyme involved in metabolism of endothelium derived nitric oxide (NO). NO's has an important role in maintaining endothelial homeostasis. Elevated ADMA levels suggest impaired endothelial function.
Time Frame	baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Serum samples were obtained and frozen but never analyzed to obtain ADMA values due to PI departure from study center prior to any batches being sent for analysis

Arm/Group Title	POMx	Control- Sugar Pill
Arm/Group Description	The POMx subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.	The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
Measure Participants	0	0

Adverse Events

Arm/Group Title	POMx		Control- Sugar Pill
Arm/Group Description	15 subjects received 1000 mg of oral POMx for 12 weeks. POMx, pomegranate polyphenol extract: 1000 mg orally once daily.		The control subjects received a matching sugar pill for 12 weeks. Sugar Pill: Matching sugar pill
All Cause Mortality
	POMx		Control- Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/7 (0%)
Serious Adverse Events
	POMx		Control- Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	POMx		Control- Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.